PROJECT SUMMARY Candidate: Yamini Virkud, MD, MA, MPH, aims to become an independent NIH-funded physician-scientist and leading expert in the field of integrated systems genomics of food allergy. To achieve this goal, she has been conducting clinical research in food allergy immunotherapy outcomes for the past 5 years, obtained a masters in biomedical sciences and a masters of public health in biostatistics, and has been working with world- renowned leaders in food allergy research. She is now a pediatric allergist and immunologist at Massachusetts General Hospital, an Instructor in Pediatrics at Harvard Medical School, and Associate Epidemiologist at Brigham & Women?s Hospital. She aims to build a career as an independent investigator by pursuing the following goals: (1) training in clinical trials and integrated network analyses of rich ?omics datasets, (2) publishing her findings and expanding her network of collaborators, (3) establishing a community of experts who are also successful mentors, (4) coursework to round out her statistical and computational educational background. This will prepare her for her first R01 application and allow her to develop her own distinct niche of integrated systems biology of food allergy. Research: The prevalence of pediatric food allergy has been increasing over the last decade, and management of food allergies is limited to avoidance of the allergen. Oral immunotherapy (OIT), the ingestion of gradually increasing amounts of allergen to protect against accidental exposure, is an investigational intervention now poised to become one of the first approved therapies for food allergy. However, individual responses to therapy vary in ways that we do not understand, and its tolerability for clinical use is primarily limited by significant allergic adverse events. This proposal details a five-year plan to provide Dr. Virkud with training to evaluate the interaction between safety and therapeutic outcomes of OIT, how these define a severe endophenotype of food allergy, the immune mechanisms underlying endophenotypes. She has proposed an innovative and strong design to address these objectives using a combination of clinical and immunologic measures, transcriptomics and metabolomics datasets. This research is intended to guide the development of a novel immunotherapy or the discovery of adjunctive therapies to improve the safety and efficacy of OIT. Environment: Dr. Virkud will conduct this research at two world-renowned institutions. She has designed a dual mentorship between Dr. Wayne Shreffler, a leader in food allergy therapeutics and immune tolerance research at Massachusetts General Hospital, and Dr. Jessica Lasky-Su, an expert in genomics and metabolomics of asthma at the Channing Division of Network Medicine, Brigham & Women?s Hospital. She has also gathered an advisory committee of experts in genetic epidemiology, including Drs. Scott Weiss, Benjamin Raby, and David Christiani. The combination of this mentorship and advisory team, along with the many resources of Harvard University, will ensure her success in transitioning towards independence.